A mental Health Clinical Research Center inpatient research unit to study affective disorders has been developed at the University of California at San Diego and at the San Diego Veterans Administration Medical Center. This clinical research unit is augmented by a cadre of MHCRC research oriented coordinating personnel and support nurses, psychology technicians and laboratory personnel, and provides a core of integrative services to MHCRC investigators. Guided by a newly strengthened scientific advisory committee, the MHCRC scientific effort has focused on the behavioral-psychopharmacologic-psychobiologic interface. The focus of the Center is on the study of affect disorders, using psychiatric patients, normals and inpatient controls. We are continuing our studies delineating differences in cholinergic function and neurohormonal response to a physostigmine challenge in subtypes of affective disorder patients and the relationship of these changes to adrenergic and serotonergic variables. We are continuing our work exploring the hypothesis that endogenous opioid polypeptides are regulatory in affective disorders, using methadone and naloxone as investigative tools. We are studying chronobiologic and photoperiodism aspects of affective disorder. Also, we are applying a high risk-low risk strategy to the study of potential prospective markers of affective disorder. We are studying behavioral mechanisms underlying tricyclic antidepressant and other neurotropic drug effects in normals and affect disorder patients, and are studying effects of various psychotropic drugs and ECT on memory and cognitive processing. Our relationship with basic scientists in the UCSD Department of Psychiatry, working on allied projects using animal models, is strong and mutually enriching. Within the above framework, multiple collaborations are proceeding.